Overview

This trial is active, not recruiting.

Condition

advanced solid tumors

Treatment

e6201

Phase

phase 1

Target

MEK

Sponsor

Eisai Inc.

Start date

June 2008

End date

December 2014

Trial size

55 participants

Trial identifier

NCT00794781, E6201-A001-102

Summary

The purpose of this study is to determine the maximum tolerated dose (MTD), safety,
tolerability, pharmacokinetics, pharmacodynamics and preliminary anti-tumor activity of
E6201 in subjects with advanced solid tumors.

Study Design

E6201 Part A (Dose Escalation): Intravenous (IV) infusion administered over 30 minutes once weekly for 3 weeks (Days 1, 8, and 15). The first 3 to 6 subjects of the first cohort will receive 20 mg/m^2/week for a cycle of 3 weeks followed by a 1-week rest period. Subsequent dose escalations may increase at increments of 100% until two Grade 2 toxicities or 1 dose-limiting toxicity (DLT) are observed in a dose group. Thereafter, doses will be increased in increments of 50% or less until the maximum tolerated dose (MTD) is determined. Part B (MTD Expansion): After the MTD is determined in Part A, 15 additional subjects will continue to receive cycles at the MTD.

Primary Outcomes

Measure

Maximum tolerated dose and dose-limiting toxicities as determined in Part A.

Secondary Outcomes

Measure

Pharmacokinetics

time frame:
Obtained prior to infusion on Day 1 of Cycle 1 (Baseline), during the infusion at 15 and 30 minutes (just prior to end of infusion), then after the end of infusion at 5 and 30 minutes, and 1, 2, 4, 8, 24, and 48 hours on Days 1 and 15 of Cycle 1 only.

Pharmacodynamics

time frame:
Prior to and post-infusion at timepoints between Days 1 and 15, and on Day 1 of Cycle 2

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria:
Subjects must meet all of the following criteria to be eligible to participate in this
study:
1. Willing and able to comply with the protocol and provide written informed consent.
2. Age greater than or equal to 18 years.
3. Histologically and/or cytologically confirmed metastatic melanoma which has
progressed after treatment with approved therapies or for which there are no standard
effective therapies available. CNS metastases from a primary melanoma are allowed.
4. Subjects must have melanoma tumor status established by a BRAF-gene analysis report
from a CLIA qualified laboratory.
5. Subjects must have at least one tumor lesion accessible to biopsy in addition to one
which is accurately and serially measurable according to RECIST 1.0 using either
CT/MRI or photography (as appropriate), and which measures greater than 1.5 cm in the
longest diameter for a non-lymph node and greater than 2.0 cm in the short axis
diameter for a lymph node.
6. Female subjects of childbearing potential must agree to use medically acceptable
methods of contraception, such as abstinence, double-barrier method (e.g., condom and
spermicide; condom, diaphragm, and spermicide), intrauterine device (IUD), or have a
vasectomised partner. Female subjects who use hormonal contraceptives must also use
an additional approved method of contraception (as described previously).
Contraceptive measures must start either prior to or at Screening and continue
throughout the entire study period and for 2 months after the last dose drug is
administered. Pregnant and/or lactating females are excluded.
7. Male subjects must agree to use contraceptive methods such as abstinence, or
double-barrier method (e.g., condom and spermicide; condom, diaphragm, and
spermicide). Contraceptive measures must start either prior to or at Screening and
continue throughout the entire study period and for 2 months after the last dose of
study drug is administered.
8. Adequate bone marrow function defined as:
- Absolute neutrophil count (ANC) greater than or equal to 1.5 x 10^9/L
- Hemoglobin greater than or equal to 9.0 g/dL; however, a hemoglobin value less
than 9.0 g/dL is acceptable if it is corrected to greater than or equal to 9.0
g/dL by growth factor or transfusion before the start of treatment
- Platelet count greater than or equal to 100 x 10^9/L.
9. Adequate renal function defined as:
- Serum creatinine less than 1.5 mg/dL or calculated creatinine clearance greater
than 50 mL/minute per the Cockcroft-Gault formula 10 Adequate liver function
defined as:
- Total Bilirubin within normal limits
- Alkaline phosphatase (AP), alanine transaminase (ALT), and aspartate
transaminase (AST) less than or equal to 2.5 x upper limit of normal (ULN)
- AP, ALT, and AST less than or equal to 5 x ULN in the case of liver metastases
and liver-specific AP less than or equal to 3 x ULN in the case of bone
metastases 11 Eastern Cooperative Oncology Group (ECOG) performance status less
than or equal to 1.
12. Life expectancy greater than 3 months.
Exclusion Criteria:
Subjects who meet any of the following criteria are not eligible to participate in this
study:
1. Known human immunodeficiency virus (HIV), clinical evidence of active viral hepatitis
B or C, or severe/uncontrolled infections or intercurrent illness that is unrelated
to the tumor.
2. Prior surgery, radiotherapy, chemotherapy, biologic therapy, or investigational
agents within 4 weeks prior to the first infusion and prior immunotherapy, hormonal,
or molecular-targeted therapy within 2 weeks prior to the first infusion. All acute
toxicities related to prior treatments should have resolved.
3. Active malignancy other than the present diagnosis within the past 24 months (except
treated non-melanoma skin cancer or carcinoma in situ of the cervix).
4. QT interval corrected for rate (QTc) greater than 450 msec on the electrocardiogram
(ECG) obtained at Screening (Day -21 to 0) using the Fridericia method for QTc
analysis.
5. History or substance or alcohol abuse which, in the opinion of the investigator,
would prohibit participation in the study.
6. History of clinically significant cardiac impairment, congestive heart failure, New
York Heart Association (NYHA) cardiac disease classification Class II, unstable
angina, or myocardial infarction during the previous 6 months, or serious cardiac
arrhythmia.
7. Current significant co-morbid disease which, in the opinion of the investigator,
would exclude the subject from the study.

Related Tags

A family of dual-specific protein kinases that are activated through phosphorylation by mitogen-activated protein kinase kinase kinase (MAP3K, MAPKKK) proteins and can subsequently phosphorylate and activate mitogen-activated protein kinases (MAPK).